Conversion of anterior limb bud cells to ZPA signaling cells in vitro and in vivo

Abstract

Following a graft of posterior (zone of polarizing activity or ZPA) cells into the anterior margin of the developing chick wing bud, anterior cells are induced to alter their developmental fate and form structures that are normally composed of posterior cells. When anterior cells are cultured under microdissociation conditions they develop ZPA signaling ability within 24 hr. ZPA signaling in these cultures is transient and once established the level of ZPA signaling declines with time in culture. ZPA signaling in anterior cells is sensitive to treatment with fibroblast growth factor-2 (FGF-2); the development of ZPA signaling is inhibited when nonsignaling anterior cells are cultured in the presence of FGF-2. Conversely, when anterior cells that have developed ZPA signaling are treated with FGF-2, ZPA signaling levels are maintained. Thus, our results suggest that FGF-2 maintains or stabilizes the positional character of anterior (nonsignaling) cells, as well as anterior ZPA signaling converted cells, and posterior (ZPA signaling) limb bud cells in vitro (R. Anderson, M. Landry, and K. Muneoka (1993) Development 117, 1421-1433). In addition, anterior cells will convert to ZPA signaling cells in vivo following apical ectodermal ridge (AER) removal, suggesting that a factor(s) localized to the AER prevents anterior cells from developing ZPA signaling capability during limb outgrowth. These findings indicate that nonsignaling anterior limb bud cells have the potential to become ZPA signaling cells and that FGF-2, or a related factor, functions in the maintenance of positional states in the developing limb. © 1994 by Academic Press, Inc.